BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis

Romano, Maria Fiammetta; Festa, Michela; Pagliuca, Gabriella; Lerose, Rosa; Bisogni, Rita; Chiurazzi, Federico; Storti, Gabriella; Volpe, Stefano; Venuta, Salvatore; Turco, Maria Caterina; Leone, Arturo

doi:10.1038/sj.cdd.4401167

Cited by 101 publications

(93 citation statements)

References 19 publications

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“…4 On the other hand, bag3 expression is constitutive in some neoplastic cell types, in which BAG3 protein appears to exert an anti-apoptotic role. From the first evidence of BAG3-mediated survival in B-CLLs, 5 a number of reports confirmed the anti-apoptotic activity of the protein in tumours of different compartments. 2,5 --20 Indeed, BAG3 down-modulation enhances apoptosis in leukaemia, 9 melanoma, 19 osteosarcoma, 19 glioblastoma 18,20 and thyroid carcinoma cells, 14 whereas its overexpression protects the cells from pro-apoptotic inputs (serum deprivation, oxidants and drugs).…”

Section: Introductionmentioning

confidence: 94%

BAG3 controls angiogenesis through regulation of ERK phosphorylation

et al. 2012

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BAG3 is a co-chaperone of the heat shock protein (Hsp) 70, is expressed in many cell types upon cell stress, however, its expression is constitutive in many tumours. We and others have previously shown that in neoplastic cells BAG3 exerts an antiapoptotic function thus favoring tumour progression. As a consequence we have proposed BAG3 as a target of antineoplastic therapies. Here we identify a novel role for BAG3 in regulation of neo-angiogenesis and show that its downregulation results in reduced angiogenesis therefore expanding the role of BAG3 as a therapeutical target. In brief we show that BAG3 is expressed in endothelial cells and is essential for the interaction between ERK and its phosphatase DUSP6, as a consequence its removal results in reduced binding of DUSP6 to ERK and sustained ERK phosphorylation that in turn determines increased levels of p21 and p15 and cell-cycle arrest in the G1 phase.

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Section: Introductionmentioning

confidence: 94%

BAG3 controls angiogenesis through regulation of ERK phosphorylation

et al. 2012

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“…Ailanthione was diluted in 10% FCS-RPMI and added to Jurkat cell cultures at the indicated concentrations ( Figure 1Aa) and for the indicated times ( Figure 1Ab); then apoptosis was evaluated by incorporation of propidium iodide in the DNA of permeabilised cells. 4 Ailanthone induced the appearance of 450% hypodiploid cells in cell cultures: its maximal effect was exerted at a concentration of 1 mg/ml and 72 h following its addition to cultures ( Figure 1A). …”

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confidence: 99%

“…a -Cells (1 Â 10 6 /ml) were incubated in 10% FCS-RPMI medium, in the presence of the indicated concentrations of ailanthone, for 24 h. Then, hypodiplody was analysed by propidium iodide incorporation in permabilised cells and flow cytometry. 4 b -Cells (1 Â 10 6 / ml) were incubated in 10% FCS-RPMI medium, in the presence of 0.13 mg/ml of ailanthone, for the indicated times, and then hypodiploidy was evaluated. (B) -Induction of mitochondrial membrane depolarization by ailanthone.…”

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confidence: 99%

Quassinoids can induce mitochondrial membrane depolarisation and caspase 3 activation in human cells

Rosati¹,

Quaranta²,

Ammirante³

et al. 2004

Cell Death Differ

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“…bag3 gene expression is constitutive in some tumor types, including leukemias; in these cells, BAG3 protein has been shown to sustain cell survival and downmodulate cell apoptotic response to drugs, by either HSP70-dependent or -independent mechanisms. [4][5][6][7] Here we report that WT1 induces bag3 gene expression. This finding identifies a novel target of WT1 protein involved in apoptosis regulation in leukemia cells.…”

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confidence: 61%